In the beginning of the story, it shows the respective heroes awakening from nightmares about the death of their loved ones (Spider-Man's sees his uncle Ben Parker murdered and when the killer reveals himself to be the Joker; Batman witnesses the death of his parents at the hands of Carnage) and it's reflection on their roles as super heroes.

In Ravencroft Institute, Spider-Man is at the institute At the behest of Dr. Ashley Kafka to oversee her as she attempts to cure Carnage from his mental condition. Despite the high-tech containment system, Carnage breaks free from his prison and battles Spider-Man, but is then stunned and reverted back to Cletus Kasady by the institute's heavily armed guards utilizing "microwave guns". Kafka is confused as to how Carnage was able resist the high intense levels of heat wave from his prison that neutralize the symbiote. She determines that the only way to neutralize the symbiote is through Kasady's mind.

Spider-Man and Kafka are greeted by Cassandra Briar, a behavioral psychologist appointed by congressional committee to deal with people such as Kasady. Their solution to Kasady's hostile mentality is to insert a bio-technic computer chip into his body to control and pacify him. However, Kafka and Spider-Man are totally against Briar's methods. They are over- ridden by Briar as her method puts an end to Kasady's terror as Carnage, while neither Kafka nor Spidey were able to solve the problem. As Briar talks to the two, Kasady is undergoing the implant surgery.

Meanwile, in Gotham City, Batman stops the Joker from unleashing Bats infected with Joker venom. Later, at Arkham Asylum, Briar and Kafka view the security footage of an imprisoned Joker in his cell from a monitor in Dr. Arkham's office. Briar consults with Arkham on using her bio-technic chip to solve Joker's insanity.

Dr. Arkham is unsure of Briar's method but is convinced when Briar surprisingly shows a pacified and timid Cletus Kasady in handcuffs. Briar fully explains to Arkham that the chip not only calmed Kasady's aggression but subjugated the symbiote into a state of dormancy because, without Kasady's violent emotions, the symbiote had nothing to feed off of and became tamed.

Sometime later, the Joker is implanted with the chip and is displayed along with Kasady in a press conference in front of Arkham Asylum as Briar praises the use of the chip. Aferwards, Briar and a driver escorts Joker and Kasady through Gotham. The driver is uneasy at having the two criminals unguarded. Briar assures him that the two are no longer the men they once were, and that "the Joker and Carnage are dead". As Briar says this, the driver is impaled by Carnage. The symbiote explains to Briar that the chip proves useless in containing him and he has been waiting for the right moment to "explode".

As the car they are in crashes, Carnage holds both Joker and Briar hostage as the guarded government escorts are at a standstill. [unclear reference as to where guards were as previous paragraph says they were unguarded] A guard then reveals himself to be Batman. Carnage shows Batman that he is entirely different from the usual Batman's Rogue's Gallery nemesis. While Carnage is talking, Spider-Man appears and saves Briar with his webs. Spider-Man and Batman attack Carnage. However, Carnage escapes along with the Joker by shooting shards of tentacles at the guards, forcing the heroes to delay and tend their wounds.

Later, Batman tells Spider-Man to stop 'helping' and leave the city. Spider-Man protests to him that he only wants to help, but Batman states again that he doesn't need or want his help and then leaves.

At a warehouse, Carnage manages to destroy the bio-technic chip within the Joker allowing him to be who he was again. Carnage then proposes that he and the Joker should work together. The Joker agrees.

At the Bat Cave, Batman researches Cletus Kasady and realizes that his psyche is too unfathomable to grasp. Batman then decides to leave to "pick up something" after implicitly disrespecting Alfred's finger sandwiches.

Meanwhile, Spider-Man swings across Gotham City and stops an insane mugger from murdering a woman and is then greeted by Batman in his Batmobile who beckons him to come with him.

In Joker's hideout in a abandoned theater, the Crown Prince of Crime explains to Carnage his plan of implanting his Joker virus in hundreds of "Joker-in-the-boxes" and to be given away to "needy tots" as their "Christmas present". However, Carnage argues against the Joker's scheme as "stupid" and prefers the more direct motive of mass-murdering people in the most horrific way. This disgusts the Joker, who proudly proclaims that "style" and "theater" are the better route. The Joker decides that teaming up with Carnage is wrong, comparing him to David Hasselhoff. After infuriating Carnage, Joker makes his leave through a trapdoor. From a safe distance, the Joker uses a remote detonator to destroy his hideout with massive explosions while Carnage is still inside.

Meanwhile, traveling in the Batmobile, Batman apologizes to Spider-Man for denying his help and that having a friend who knew about Carnage may prove helpful in arresting the symbiote. The two manage to track Carnage's location through a remnant of his chip by tracking its frequency, and discovers the ruined theater. The two discover the body of Carnage but it proves to be a trap, as Carnage grabs hold of Batman, who tells Carnage he'd rather die than submit.

As Carnage is poised to make the killing blow on Batman, the Joker interrupts and tells Carnage to back off from killing Batman, as he is the only one to has the right to kill "his" Batman. Joker reveals this Joker-in-the-Box containing the deadly virus, announcing his plans to unleash it immediately. Spider-Man expresses shock at Joker's mindless disregard for human life, while Carnage displays abject fear of being killed, giving Batman the edge in combat with the cowardly villain. Spider-Man then snatches the Joker-in-the-Box from the Joker with his webshooter, as Batman subdues a "weak-minded" Carnage into submission, forcing him to revert back to Kasady. Spider-Man tracks down Joker and grabs hold of him, and threatens to kill him, which delights Joker, who is eager at the chance at driving a "goody two shoes" into cold-blooded murder. Spider-Man relents, releasing Joker, and taking him down with a punch, knocking him into unconsciousness.

With the defeat of both Carnage and the Joker, both Batman and Spider-Man thank each other, wordlessly with a handshake. Spider-Man swings off, returning to New York, as Batman watches over Gotham.